Systemic target therapeutic drugs, such as sorafenib, lenvatinib, or regorafenib are the only drugs that are known to be effective against advanced hepatocellular carcinoma (HCC). However, these agents show a limited efficacy in killing residual tumors. Immunotherapy is an alternative approach to this treatment and has been used to successfully treat different cancers, including HCC. HCC is an inflammation-induced cancer and represents a very interesting target for immunotherapeutics. Immunotherapies aim to reverse the immune tolerance and suppression found in tumor microenvironments and include approaches, such as adoptive cell therapy, immune checkpoint inhibition, and cancer vaccination. Adoptive cell therapy uses autologous natural killer or cytokine-induced killer cells by cultivating them ex vivo and subsequently reinfusing them into the patient. Immune checkpoint inhibitors reactivate tumor-specific T cells by suppressing checkpoint-mediated inhibitory signaling. Cancer vaccination induces a tumor-specific immune response by activating effector T lymphocytes. A wide range of potential immunotherapy-related adverse events occur; therefore, a multidisciplinary collaborative management is required across the clinical spectrum. This review summarizes the current status of immunotherapy for HCC and provides a perspective on its future applications.
Carcinoma, Hepatocellular ; Cell- and Tissue-Based Therapy ; Cytokine-Induced Killer Cells ; Homicide ; Humans ; Immune Tolerance ; Immunotherapy ; Neoplasm, Residual ; Oncolytic Viruses ; T-Lymphocytes ; Tumor Microenvironment ; Vaccination

Objective: : The goal of the following statewide age and gender-coordinated cohort study in Korea is to find out if there is a link between acute myocardial infarction (AMI) and Parkinson’s disease (PD). Methods: : Utilizing the National Health Insurance Sharing Service cohort, patient data were collected. Six thousand four hundred seventy-five individuals with PD were distinguished by utilizing the International Classification of Diseases 10 code G20 and have enrolled in the PD group. The number of participants decreased to 5259 after excluding 1039 patients who were hospitalized less than one time or who visited an outpatient clinic less than twice. Then, 26295 individuals were selected as part of the control group after case control matching was conducted through 1 : 5 age- and gender-coordinated matching. The Cox proportional hazard regression analysis and Kaplan-Meier method were utilized to analyze the likelihood of AMI in PD. Results: : After controlling for age and gender, the hazard ratio of AMI in the PD group was 3.603 (95% confidence interval [CI], 2.837–4.577). After that, the following hazard ratio of AMI in the PD group was modified against for co-morbid medical disorders, resulting in 3.551 (95% CI, 2.795–4.511). According to a subgroup analysis, in males and females aged <65 and aged ≥65 and in the non-diabetes and diabetes, hypertension and non-hypertension, dyslipidemia and non-dyslipidemia subgroups, the AMI incidence rates were dramatically higher in the PD group compared to that of the control. Conclusion : Individuals with PD have a greater chance of AMI, according to this cross-national study.

No abstract available.
Thymoma*

BACKGROUND: We utilized diffusion tensor imaging (DTI) to evaluate the cerebral white matter changes that are associated with phantom limb pain in patients with unilateral arm amputation. It was anticipated that this would complement previous research in which we had shown that changes in cerebral blood volume were associated with the cerebral pain network. METHODS: Ten patients with phantom limb pain due to unilateral arm amputation and sixteen healthy age-matched controls were enrolled. The intensity of phantom limb pain was measured by the visual analogue scale (VAS) and depressive mood was assessed by the Hamilton depression rating scale. Diffusion tensor-derived parameters, including fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD), were computed from the DTI. RESULTS: Compared with controls, the cases had alterations in the cerebral white matter as a consequence of phantom limb pain, manifesting a higher AD of white matter in both hemispheres symmetrically after adjusting for individual depressive moods. In addition, there were associations between the RD of white matter and VAS scores primarily in the hemispheres related to the missing hand and in the corpus callosum. CONCLUSIONS: The phantom limb pain after unilateral arm amputation induced plasticity in the white matter. We conclude that loss of white matter integrity, particularly in the hemisphere connected with the missing hand, is significantly correlated with phantom limb pain.
Amputation ; Anisotropy ; Arm ; Blood Volume ; Brain ; Chronic Pain ; Complement System Proteins ; Corpus Callosum ; Depression ; Diffusion ; Diffusion Tensor Imaging ; Hand ; Humans ; Magnetic Resonance Imaging ; Neuronal Plasticity ; Phantom Limb ; Plastics ; White Matter

OBJECTIVE: To develop a new tool for aspiration risk prediction based on pharyngeal width at rest in older adults with symptoms of aspiration. METHODS: Lateral cervical spine roentgenograms were obtained from 33 older adult patients who complained of dysphagia and from 33 healthy, age-matched controls. Pharyngeal width at rest was measured at two points. We named the average of these two pharyngeal widths ‘JOSCYL Width’, calculated ‘JOSCYL Scale’, and compared these parameters between dysphagia and control groups. Correlations of individual JOSCYL Width and JOSCYL Scale, with Penetration Aspiration Scale (PAS) and Dysphagia Outcome and Severity Scale (DOSS) scores were analyzed for the dysphagia group. To determine optimal cutoff points for predicting aspiration, a receiver operating characteristic curve analysis was performed on JOSCYL Width and JOSCYL Scale. RESULTS: Both JOSCYL Width and JOSCYL Scale of the dysphagia group were larger than those of the control group (p<0.001). The correlation between JOSCYL Width and severity of dysphagia was significant for the dysphagia group (PAS p=0.007; DOSS p=0.012). The correlation between JOSCYL Scale and the severity of dysphagia was also significant for the dysphagia group (PAS p=0.009; DOSS p=0.011). Optimal cutoffs for JOSCYL Width and JOSCYL Scale for predicting aspiration were 20.0 mm and 5.9, respectively. CONCLUSION: JOSCYL Width and JOSCYL Scale can be new indicators for predicting aspiration in older adults. They are both precise and easy to use.
Adult ; Aged ; Deglutition Disorders ; Dioctyl Sulfosuccinic Acid ; Humans ; Pharynx ; ROC Curve ; Spine

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung.Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods: and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P ), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. Conclusions Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

Purpose: Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi. Materials and Methods: After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition. Results: In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9−57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5−53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002). Conclusion Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction.

Purpose: Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi. Materials and Methods: After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition. Results: In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9−57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5−53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002). Conclusion Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction.

Objectives: The aim of this study is to determine whether there is a difference between right and left femur bone mineral density (BMD) in postmenopausal women. Methods: We performed a retrospective chart review of postmenopausal women who underwent bone mineral density (BMD) measurement from 2010 to 2019 at a single center using dual-energy X-ray absorptiometry (DXA). Data, including BMD and T-scores of bilateral hip and lumbar spine, was gathered for all postmenopausal women above the age of 50 years. The continuous variables were expressed as means with standard deviation for normal distribution and analyzed with a two-sample t-test. Multiple regression analysis was used to test the effect of underlying medical conditions on T-score of bilateral hips. For all analyses, a p-value of ＜0.05 was considered significant. Results: 346 patients were included in the study with a mean age at imaging of 62 + 9.7 years and body mass index (BMI) of 23.4 + 6.1 kg/m2 . There were no significant differences between right and left femoral BMDs in all patients. There were significant differences in BMD of both total femurs in women in their 60s and women with normal BMD. There was no difference in both femur BMDs between those taking hormone therapy and those not taking hormone therapy. In patients undergoing osteoporosis treatment, there was a difference in the BMD of both femur neck. Calcium and vitamin D intake were not associated with differences between both femur BMD. We found a significant correlation between the BMD measures at lumbar spine and both femur (p ＜ 0.01). Conclusion There were no significant differences between right and left femoral BMDs in postmenopausal women. Therefore, BMD may be measured at either hip. The correlation of bone density between lumbar spine and femur neck is shown to be statistically meaningful. Based on the knowledge of the correlation coefficients between lumbar spine and femur neck, it seems possible to predict the BMD result of one location through the measurement of another.

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways.Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC BMP2 ) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC BMP2 were associated with migration and growth. MSC BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC BMP2 . MSC BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3 + CD25 + Treg of CD4 + cells were further increased in ALI mice treated with MSC BMP2 . In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC BMP2 . Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.